Dexamethasone alters sleep and fatigue in pediatric patients with acute lymphoblastic leukemia

BACKGROUND: Dexamethasone improves the cure rate of childhood acute lymphoblastic leukemia (ALL) but causes physical and behavioral adverse events. The objective of the current study was to determine the effect of dexamethasone exposure on sleep and fatigue in pediatric patients with ALL. METHODS: One hundred pediatric patients with low-risk or standard-risk ALL were enrolled on 1 of 3 protocols (St. Jude Total XV, Children's Oncology Group [COG] 9904, or COG 9905) at 3 institutions. The mean age of the cohort was 9.24 +/- 3.23 years (range, 5.03-18.14 years). The majority of patients were white (79%) males (62%) with standard-risk ALL (63%). The cohort was divided into 4 subgroups: St. Jude low-risk, St. Jude standard-risk, COG low-risk, and COG standard-risk. Patients wore a wrist actigraph to monitor sleep activity during 2 consecutive 5-day periods: During the first period, they did not receive dexamethasone; and, during the second period, they did. Patients and their parents completed fatigue instruments on Days 2 and 5 of each period, and parents completed sleep diaries. RESULTS: Actual sleep minutes, sleep duration, total daily nap minutes, and fatigue increased significantly during the dexamethasone treatment for 3 to 4 of the subgroups. Total daily nap minutes increased significantly for both standard-risk groups during the dexamethasone treatment. Parents reported significant increases in their child's nighttime awakenings, restless sleep, and nap time during dexamethasone treatment. CONCLUSIONS: Dexamethasone treatment during continuation therapy for childhood ALL significantly and adversely altered sleep and fatigue, confirming that sleep and fatigue are behavioral responses to dexamethasone.     

Effect of Pre-treatment of α-Ketoglutarate on Cyanide-induced Toxicity and Alterations in Various Physiological Variables in Rodents

Objective To investigate the effects of pre-treatment of α-ketoglutarate (α-KG) on cyanide-induced lethality and changes in various physiological parameters in rodents. Methods The LD50 of potassium cyanide (KCN) given orally (po), intraperitoneally (ip), subcutaneously (sc) or intravenously (iv) was determined in male mice, in the presence or absence α-KG given po, ip or iv. α-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg by po or ip route, and at 0.10, 0.20 or 0.40 g/kg by iv route. Protection index (PI) was calculated as the ratio of LD50 of KCN in the presence of α-KG (protected animals) and LD50 of KCN in the absence of α-KG (unprotected animals). In a separate experiment, several physiological variables viz. mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), neuromuscular transmission (NMT) and rectal temperature (RT) were measured in anesthetized female rats pre-treated (-10 min) with po (2.0 g/kg) or iv (0.125 g/kg) α-KG and then administered sub-lethal (0.75 LD50) or lethal (2.0, 4.0 or 8.0 LD50) doses of KCN (po). Results PI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and 6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with α-KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for 0.50, 1.0 and 2.0 g/kg α-KG given ip (-10 min), respectively. A lower PI of 3.37, 2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg α-KG given ip at -10, -20 or -40 min, respectively. Similarly, a PI of 3.37, 2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg α-KG given po at -10, -20 or -40 min, respectively. No appreciable protection was observed when lower doses of α-KG (ip or po) challenged KCN given by sc route. Pre-treatment of iv or po administration of α-KG did not afford any protection against KCN given po or iv route. Oral treatment of 0.75 LD50 KCN caused significant decrease in MAP and HR after 15 min, RR after 30 min and NMT after 60 min. There was no effect on RT. No reduction in MAP, HR, RR and RT was observed when rats received 2.0 or 4.0 LD50 KCN after pre-treatment of α-KG (po; 2.0 g/kg). However, no protection was observed on NMT. Protective efficacy of α-KG was not observed on MAP, HR, RR, and NMT decreased by 8.0 LD50 KCN. Decrease in MAP and NMT caused by 2.0 LD50 KCN (po) was resolved by iv administration of α-KG. Conclusions Cyanide antagonism by α-KG is best exhibited when both α-KG and KCN are given by po route. The protective effect of α-KG on cyanide-induced changes in several physiological parameters also indicates a promising role of α-KG as an alternative cyanide antidote.     

Extent of error in estimating nutrient intakes from food tables versus laboratory estimates of cooked foods

Individual cooked foods (104) and composite meals (92) were examined for agreement between nutritive value estimated by indirect analysis (E) (Indian National database of nutrient composition of raw foods, adjusted for observed moisture contents of cooked recipes), and by chemical analysis in our laboratory (M). The extent of error incurred in using food table values with moisture correction for estimating macro as well as micronutrients at food level and daily intake level was quantified. Food samples were analyzed for contents of iron, zinc, copper, beta-carotene, riboflavin, thiamine, ascorbic acid, folic acid and also for macronutrients, phytate and dietary fiber. Mean percent difference in energy content between E and M was 3.07+/-0.6%, that for protein was 5.3+/-2.0%, for fat was 2.6+/-1.8% and for carbohydrates was 5.1+/-0.9%. Mean percent difference in vitamin contents between E and M ranged from 32 (vitamin C) to 45.5% (beta-carotene content); and that for minerals between 5.6 (copper) to 19.8% (zinc). Percent E/M were computed for daily nutrient intakes of 264 apparently healthy adults. These were observed to be 108, 112, 127 and 97 for energy, protein, fat and carbohydrates respectively. Percent E/M for their intakes of copper (102) and beta-carotene (114) were closer to 100 but these were very high in the case of zinc (186), iron (202), and vitamins C (170), thiamine (190), riboflavin (181) and folic acid (165). Estimates based on food composition table values with moisture correction show macronutrients for cooked foods to be within +/- 5% whereas at daily intake levels the error increased up to 27%. The lack of good agreement in the case of several micronutrients indicated that the use of Indian food tables for micronutrient intakes would be inappropriate.     

Cirumstances and motivations for seeking abortions: a community based study in Chandrapur District, Maharashtra

The present population based group comparison study was undertaken to study the circumstances, motivations and influencing factors for seeking abortion in women in Chandrapur District of Maharashtra. Participants of the study included 500 cases of induced abortion and the equal number of normal delivered women during the same period and in the same area as comparison group. Having two children, domestic problems and unwanted pregnancy were conditions acceptable to study subjects to terminate the pregnancy. Family and domestic problems, poor socio-economic status, short inter-pregnancy interval and completed family size were some of the important reasons quoted by study subjects for not desiring to continue the current pregnancy. Majority of the subjects felt that the decision to terminate or keep pregnancy is usually taken jointly by both the husband and wife. Family and domestic problems, poor socioeconomic status and short inter pregnancy interval were the important reasons quoted by abortion cases for seeking abortion in the current pregnancy. Only 1.80% of the cases reported failure of contraceptive method as a cause of seeking abortion services. In 78.4% of abortion cases as compared to 5.4% subjects from the comparison group, pregnancy was un-planned.     

Masked Hypertension and Elevated Nighttime Blood Pressure in CKD: Prevalence and Association with Target Organ Damage

Background and objectives

Masked hypertension and elevated nighttime BP are associated with increased risk of hypertensive target organ damage and adverse cardiovascular and renal outcomes in patients with normal kidney function. The significance of masked hypertension for these risks in patients with CKD is less well defined. The objective of this study was to evaluate the association between masked hypertension and kidney function and markers of cardiovascular target organ damage, and to determine whether this relationship was consistent among those with and without elevated nighttime BP.

Design, setting, participants, & measurements

This was a cross-sectional study. We performed 24-hour ambulatory BP in 1492 men and women with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. We categorized participants into controlled BP, white-coat, masked, and sustained hypertension on the basis of clinic and 24-hour ambulatory BP. We obtained echocardiograms and measured pulse wave velocity in 1278 and 1394 participants, respectively.

Results

The percentages of participants with controlled BP, white-coat, masked, and sustained hypertension were 49.3%, 4.1%, 27.8%, and 18.8%, respectively. Compared with controlled BP, masked hypertension independently associated with low eGFR (−3.2 ml/min per 1.73 m²; 95% confidence interval, −5.5 to −0.9), higher proteinuria (+0.9 unit higher in log₂ urine protein; 95% confidence interval, 0.7 to 1.1), and higher left ventricular mass index (+2.52 g/m^2.7; 95% confidence interval, 0.9 to 4.1), and pulse wave velocity (+0.92 m/s; 95% confidence interval, 0.5 to 1.3). Participants with masked hypertension had lower eGFR only in the presence of elevated nighttime BP (−3.6 ml/min per 1.73 m²; 95% confidence interval, −6.1 to −1.1; versus −1.4 ml/min per 1.73 m²; 95% confidence interval, −6.9 to 4.0, among those with nighttime BP <120/70 mmHg; P value for interaction with nighttime systolic BP 0.002).

Conclusions

Masked hypertension is common in patients with CKD and associated with lower eGFR, proteinuria, and cardiovascular target organ damage. In patients with CKD, ambulatory BP characterizes the relationship between BP and target organ damage better than BP measured in the clinic alone.     

Multivessel total arterial revascularization via left thoracotomy

Off-pump coronary artery bypass grafting is now becoming the preferred method of coronary revascularization. The trend is towards complete revascularization, preferably arterial. We are describing here a method of multivessel, total arterial, complete revascularization via an anterolateral thoracotomy approach in 27 patients. There was an average of 3.2 grafts/patient. Angiograms were performed in 9 patients (33.33 %). There were no operative mortalities. None of the patients required conversion to cardiopulmonary bypass or midsternotomy.     

Nanometer-scale mapping and single-molecule detection with color-coded nanoparticle probes

We report a method for single-molecule detection and biomolecular structural mapping based on dual-color imaging and automated colocalization of bioconjugated nanoparticle probes at nanometer precision. In comparison with organic dyes and fluorescent proteins, nanoparticle probes such as fluorescence energy-transfer nanobeads and quantum dots provide significant advantages in signal brightness, photostability, and multicolor-light emission. As a result, we have achieved routine two-color superresolution imaging and single-molecule detection with standard fluorescence microscopes and inexpensive digital color cameras. By using green and red nanoparticles to simultaneously recognize two binding sites on a single target, individual biomolecules such as nucleic acids are detected and identified without target amplification or probe/target separation. We also demonstrate that a powerful astrophysical method (originally developed to analyze crowded stellar fields) can be used for automated and rapid statistical analysis of nanoparticle colocalization signals. The ability to rapidly localize bright nanoparticle probes at nanometer precision has implications not only for ultrasensitive medical detection but also for structural mapping of molecular complexes in which individual components are tagged with color-coded nanoparticles.